The mechanisms of action of the DNA reactive drugs: chloroethylnitrosoureas, AZQ, cis-Pt, and May&Baker 39565 have been investigated in human normal and tumor cell lines in vitro. The role of the repair of DNA chloroethyl monoadducts has been studied by inhibiting the repair protein with MNNG. Filter techniques have been developed to quantitate the number of potentially crosslinkable sites in DNA. These techniques should allow the study of adduct repair and its relationship to differential cytotoxicity of antitumor agents.